The results of these studies indicate that the corneal endothelium (rabbit and human) can maintain its barrier function over a pH range of 6.8 to 8.8. A pH below and above that range will result in direct cellular damage. Therefore any drug vehicle or irrigation solution used within the eye should be within this range in order to prevent cellular damage to the intraocular tissue. Our studies have established that phenylephrine can cause a drug induced edema and that there is a cytotoxic effect on the corneal endothelium and keratocytes when used in corneas where the epithelium has been removed. In corneas with an intact epithelium the damage was less severe and limited to the epithelium. Phenylephrine, topical anesthesia and epithelial scraping can also cause a reduction in stroma and endothelial glucose metabolism with the greatest decrease occurring with the 10% phenylephrine. The data on the measurement of the hexose-monophosphate shunt provides evidence for the first time that HMS exist in the corneal endothelium and may indeed be the metabolic mechanism by which the endothelium can handle metabolic and chemical oxidative stresses. Studies with the effects of Ca ions ionophore illustrate that corneal endothelial intracellular Ca ions can be mobilized by ionophores, which can preserve endothelial junctional complexes and in turn the barrier function of the endothelium. Following vitrectomy in normal rabbits, steady state values for the composition of intraocular fluids is reestablished in 110 days provided that there are no intravitreal membranes. Finally, the studies on the buphthalmic rabbit cornea and the marine teleost cornea indicate that both of these tissues are under metabolic stress and may serve as good models to study the metabolic pathways that may be present in diseased or stressed human corneas.